1. Field of the Invention
The present invention relates to antibody specific for cotinine, and antibody specific for nicotine. The present invention also relates to the field of treating nicotine addiction.
2. General Background and State of the Art
Nicotine is a naturally occurring alkaloid found in many plants. The principal source of nicotine exposure is through the use of tobacco. Nicotine is an amine composed of pyridine and pyrrolidine rings and crosses biological membranes and the blood brain barrier easily. The absorbed nicotine is extensively metabolized in the liver to form a wide variety of metabolites by the mixed function of oxidase system. Though nicotine has been shown to affect a wide variety of biological functions ranging from gene expression to regulation of hormone secretion and enzyme activities, nicotine is known to induce addiction. But nicotine has a relatively short half-life, approximately 2 hours, which is not sufficient to induce immunogenicity.
Cotinine is the principal proximate metabolite of nicotine, and 70˜80% of nicotine absorbed is converted to cotinine prior to metabolizing into other metabolites in the liver, has a half-life of approximately 20 hours. Cotinine can be measured in a number of biological fluids including blood, saliva, urine, semen and cervical exudates. Cotinine is sufficiently sensitive to be detected also in the body fluids of those individuals, exposed to passive or environment tobacco smoke and this was why cotinine-antibody was made first and it showed the possibility of cross-reactivity for nicotine. Furthermore, in particular by gene modification of heavy chain CDR3 (HCDR3), nicotine-specific antibody can be produced from cotinine-specific antibody.
In the present study, we for the first time generated a rabbit/human chimeric monoclonal antibody specific to cotinine that contains rabbit heavy chain (VH) and light chain (VL) variable domain and human heavy chain (CH1) and light chain (CL) constant domain from the synthesized antibody library. This antibody also shows cross-reactivity with nicotine and these results indicate generation of antibody that is specific to nicotine only by the modification of the HCDR3 gene. The present invention provides a therapeutic monoclonal antibody to treat nicotine addiction.